Developing biosimilars

New active substance

The gene is isolated from human cells after which it is introduced into other carrier or vector cells (like bacteria or yeasts) that proliferate and produce large amounts of the desired compound.⁹ One it has been established that the compound can be reliably produced in sufficient amounts and initial safety and quality concerns have been addressed, the product will be tested for safety and efficacy in humans.

The development process for a biosimilar is significantly different from that of a biologic. A biologic will be a new active substance when it is first introduced to the market with no previous knowledge of safety and efficacy, while a biosimilar builds on the knowledge of safety and efficacy from years of clinical use of the reference medicine. The fundamental principle underlying the development of any biosimilar is therefore comparability with the reference (or original) product. Throughout the development process of a biosimilar, data is generated to demonstrate that the biosimilar is in all essential aspects (safety, quality, and efficacy) similar to the reference product and hence that it can be used interchangeably.^1,2,3

Production sequence

All biopharmaceuticals (inclusive of both biologics and biosimilars) are produced by living organisms or cells. These organisms range from bacteria, yeasts, and viruses to other animal cells. Establishing the appropriate cell culture, cell banks clone, fermentation and development process may take 5 years or more. Clinical trials to establish the safety and efficacy in human patients may only be initiated 6 years or more after the initial work in the laboratory was first undertaken.^1,2

Stages of development

Once the initial laboratory work has been concluded, highly sophisticated analytical and validation tools are utilised to provide a detailed characterisation of a biosimilar product to enable the above-mentioned comparability exercise.¹ Such analytical methods may include the use of peptide mapping, mass spectrometry, and assays in cells to determine the physicochemical and functional properties (e.g., molecular structure, protein modifications, and biological activity) of the biosimilar in question.³

In addition to the above, non-clinical (in a laboratory or, in exceptional cases, in animals) and clinical (in humans) studies may be conducted to establish comparative clinical safety and efficacy beyond any doubt.¹ The amount of non-clinical data required will be determined by the outcome of the quality studies. Whereas conventional clinical trials will be done to demonstrate efficacy and safety of biologicals for all therapeutic indications, clinical trials for biosimilars will be designed to compare the two products and to exclude any clinically meaningful differences.³